Clinical and therapeutic potential of protein kinase PKR in cancer and metabolism.

The protein kinase R (PKR, also called EIF2AK2) is an interferon-inducible double-stranded RNA protein kinase with multiple effects on cells that plays an active part in the cellular response to numerous types of stress. PKR has been extensively studied and documented for its relevance as an antiviral agent and a cell growth regulator. Recently, the role of PKR related to metabolism, inflammatory processes, cancer and neurodegenerative diseases has gained interest. In this review, we summarise and discuss the involvement of PKR in several cancer signalling pathways and the dual role that this kinase plays in cancer disease. We emphasise the importance of PKR as a molecular target for both conventional chemotherapeutics and emerging treatments based on novel drugs, and its potential as a biomarker and therapeutic target for several pathologies. Finally, we discuss the impact that the recent knowledge regarding PKR involvement in metabolism has in our understanding of the complex processes of cancer and metabolism pathologies, highlighting the translational research establishing the clinical and therapeutic potential of this pleiotropic kinase.

[Pet ownership and health status of pets from immunocompromised children, with emphasis in zoonotic diseases]. / Tenencia y estado de salud de mascotas de niños inmunocomprometidos, con énfasis en enfermedades zoonóticas.

OBJECTIVE: To characterize pet ownership and pet health status in families of immunocompromised (IS) children, with emphasis in zoonotic diseases. POPULATION AND METHODS: Families of IS children from two hospitals in Santiago, Chile, were interviewed and their pets were evaluated by veterinary examination, coproparasitologic and skin dermatophytes test. In specific cases, other laboratory tests were performed in IS children or their relatives. RESULTS: 47 out of 70 contacted families had pets, 42 participated in the study. Several risk factors for IS children were observed, as having a turtle as a pet and to clean cat or turtle faeces. Lack of adequate veterinary control, immunizations and deparasitation of pets were observed. Some animals showed zoonotic diseases or agents, as Brucella canis, Cryptosporidium sp, Giardia intestinalis, Toxocara canis and scabies. 44% of dogs had ticks and 37% had fleas, both potential vectors of infections. CONCLUSIONS: Our results suggest that policies to provide safer pet contact in IS children are needed.

Tenencia y estado de salud de mascotas de niños inmunocomprometidos, con énfasis en enfermedades zoonóticas / Pet ownership and health status of pets from immunocompromised children, with emphasis in zoonotic diseases

Objetive: To characterize pet ownership and pet health status in families of immunocompromised (IS) children, with emphasis in zoonotic diseases. Population and Methods: Families of IS children from two hospitals in Santiago, Chile, were interviewed and their pets were evaluated by veterinary examination, coproparasitologic and skin dermatophytes test. In specific cases, other laboratory tests were performed in IS children or their relatives. Results: 47 out of 70 contacted families had pets, 42 participated in the study. Several risk factors for IS children were observed, as having a turtle as a pet and to clean cat or turtle faeces. Lack of adequate veterinary control, immunizations and deparasitation of pets were observed. Some animals showed zoonotic diseases or agents, as Brucella canis, Cryptosporidium sp, Giardia intestinalis, Toxocara canis and scabies. 44 percent of dogs had ticks and 37 percent had fleas, both potential vectors of infections. Conclusions: Our results suggest that policies to provide safer pet contact in IS children are needed.

Objetivo: Caracterizar la tenencia y estado de salud de mascotas de niños inmunocomprometidos (IC), con énfasis en situaciones y agentes infecciosos de potencial riesgo para la salud del niño. Población y Métodos: Se entrevistó a familias de niños IC en tratamiento en dos hospitales de Santiago y se evaluó la salud de sus mascotas mediante examen clínico veterinario, copro-parasitológico y búsqueda de dermatofitos en el pelaje. En casos puntuales, se realizaron algunos exámenes de laboratorio específicos a los niños o sus familiares. Resultados: 47 de 70 familias contactadas tenían mascotas, 42 participaron del estudio. Se detectaron situaciones de alto riesgo para niños IC como poseer tortuga como mascota y limpiar excretas de gatos y tortugas. Se evidenció una mínima adherencia al control veterinario, inmunizaciones y desparasitación de mascotas. Se identificaron animales con enfermedades o agentes con potencial zoonótico, destacando Brucella canis, Cryptosporidium sp, Giardia intestinalis, Toxocara canis y sarna sarcóptica. Un 44 por ciento de los perros presentaban garrapatas y 37 por ciento pulgas, ambos potenciales vectores de infecciones. Conclusiones: Los resultados sugieren que en nuestro medio es necesario implementar medidas que permitan una tenencia más segura de las mascotas en contacto con niños IC.

[Acute retinal necrosis: an adult disease visits pediatrics]. / Necrosis retinal aguda: Una entidad de adultos en pediatría.

Acute retinal necrosis (ARN) is a serious condition that can impair vision. It mostly occurs in adult patients, especially those severely immunocompromised, in association with a reactivation of a herpes virus infection. Clinical and ophtalmological features of ARN and recommended diagnostic and management strategies are reviewed.

Necrosis retinal aguda: Una entidad de adultos en pediatría / Acute retinal necrosis: An adult disease visits pediatrics

La necrosis retinal aguda (NRA) es una afección grave que amenaza la visión. Se presenta en adultos, en especial aquellos profundamente inmunocompro-metidos, como consecuencia de la reactivación de virus del grupo herpes. Se revisan la entidad clínica de la NRA, su diagnóstico nosológico y etiológico, como el manejo recomendado actualmente.

Acute retinal necrosis (ARN) is a serious condition that can impair vision. It mostly occurs in adult patients, especially those severely immunocompromised, in association with a reactivation of a herpes virus infection. Clinical and ophtalmological features of ARN and recommended diagnostic and management strategies are reviewed.

Selective transmission of R5-tropic HIV type 1 from dendritic cells to resting CD4+ T cells.

In an in vitro coculture model of monocyte-derived, cultured human dendritic cells (DC) with autologous CD4(+) resting T cells, CCR5 (R5)-tropic strains of HIV-1, but not CXCR4 (X4)-tropic strains, were transmitted to resting CD4+ T cells, leading to prolific viral output, although DC were susceptible to infection with either strain. Macrophages, which were also infectable with either R5- or X4-tropic strains, did not transmit infection to CD4+ cells. Highly productive HIV infection in this model appeared to be a consequence of heterokaryotic syncytium formation between infected DC and T cells since syncytia formation developed only in R5-infected DC/CD4+ cocultures. These results suggested that the unique microenvironment derived from the fusion between the infected DC and CD4+ cell was highly permissive and selective for replication of R5-tropic viruses. The apparent selectivity for R5-tropic strains in such syncytia was attributable neither to differential DC-mediated activation nor to selective modulation of induction of alpha- or beta-chemokines in the infected DC. This model of HIV replication may provide useful insights into in vitro correlates of HIV pathogenicity.

Lasting effects of transient postinoculation tenofovir [9-R-(2-Phosphonomethoxypropyl)adenine] treatment on SHIV(KU2) infection of rhesus macaques.

SHIV(KU2) replicates to high levels in inoculated macaques and reproducibly causes an acute depletion of CD4(+) T cells. We evaluated the ability of treatment with the antiretroviral drug 9-R-(2-phosphonomethoxypropyl)adenine (PMPA; tenofovir), begun 7 days postinoculation, to inhibit viral replication and associated pathogenesis. Highly productive infection (plasma viral RNA > 10(6) copy eq/mL) was present and CD4 depletion had started when treatment was initiated. PMPA treatment was associated with a rapid decline in plasma viral RNA to undetectable levels, with parallel decreases in the infectivity of plasma and infectious cells in PBMCs and CSF and stabilization of CD4(+)T-cell levels. Viral dynamics parameters were calculated for the initial phase of exponential viral replication and the treatment-related decline in plasma viremia. Following cessation of treatment after 12 weeks, plasma viral RNA was detectable intermittently at low levels, and spliced viral transcripts were detected in lymph nodes. Although treatment was begun after viral dissemination, high viremia, and CD4 decreases had occurred, following withdrawal of PMPA, CD4(+) T-cell counts normalized and stabilized in the normal range, despite persistent low-level infection. No PMPA-resistance mutations were detected. These results validate the similar viral replicative dynamics of SHIV(KU2) and HIV and SIV, and also underscore the potential for long-term modulation of viral replication patterns and clinical course by perturbation of primary infection.